RTA 744 Injection in Patients With Leptomeningeal Disease

This study has been completed.
Sponsor:
Collaborator:
Reata Pharmaceuticals, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00512460
First received: August 3, 2007
Last updated: July 26, 2012
Last verified: July 2012
  Purpose
  1. The primary objectives of this study are:

    1. To determine the tolerability of RTA 744 Injection in patients with leptomeningeal disease (LMD) secondary to any type of primary tumor.
    2. In a selected group of 6-10 patients who will receive RTA 744 at or near the maximum tolerated dose (MTD), to characterize the multiple-dose pharmacokinetics of RTA 744 in plasma and CSF.
  2. The secondary objectives of this study are:

    1. To document any potential antitumor activity of RTA 744 in this patient population.
    2. To correlate pharmacokinetic information with clinical (efficacy and safety) responses, as a possible help in selecting appropriate doses for later studies.

Condition Intervention Phase
Neoplastic Meningitis
Solid Tumor
Lymphoma
Leukemia
Brain Tumor
Drug: RTA 744
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Safety and Pharmacokinetic Study of Intravenous RTA 744 Injection in Patients With Recurrent, Progressive or Refractory Neoplastic Meningitis

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • To study the highest tolerable dose of RTA 744 that can be given to patients with cancer that has spread to the meninges of the brain or the spine. [ Time Frame: 3 Years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To study the level of effectiveness of RTA 744 on the disease. [ Time Frame: 3 Years ] [ Designated as safety issue: Yes ]

Enrollment: 7
Study Start Date: September 2006
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RTA 744 Drug: RTA 744
4.8 mg/m^2 by vein Over 2 Hours On Days 1-3.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age >/=18 years.
  2. Histologic confirmation of primary malignancy at original diagnosis. All primary tumor types may be enrolled into the study (solid tumor, lymphoma, leukemia, or brain malignancy).
  3. Neoplastic meningitis/leptomeningeal metastasis refractory to conventional intrathecal therapy and defined as presence of tumor cells on cytology after cytospin, OR neuroimaging evidence of leptomeningeal tumor by MRI accompanied by clinical evidence of leptomeningeal tumor.
  4. Patient is not eligible for higher priority clinical trial.
  5. If patient had surgical resection prior to enrollment, at least 2 weeks should have elapsed prior to enrollment into the study and patient must have completely recovered from the side effects of such therapy.
  6. For those patients taking steroid medications, the dose of steroid should be stable for at least 7 days prior to obtaining the Gd-MRI of the brain and spine, if medically feasible.
  7. Karnofsky Performance Status (KPS) of >/= 60.
  8. Laboratory Parameters: 1) Absolute Neutrophil Count (ANC) >/=1.5 x 10^9/L; 2) Hemoglobin (Hgb) >/=9 g/dl; 3) Platelets >/= 100 x 10^9/L; 4) AST and ALT </= 3.0 x Upper Limit of Normal (ULN); 5) Serum bilirubin </= 1.5 x ULN; 6) Serum creatinine </= 1.5 x ULN and 24 hour creatinine clearance >/= 50 ml/min
  9. Life expectancy of at least 8 weeks based on the judgment of the clinical investigator.
  10. Written informed consent obtained.

Exclusion Criteria:

  1. Concurrent intrathecal or intraventricular therapy for leptomeningeal disease or other malignancy.
  2. Concurrent oral or intravenous cytotoxic therapy for leptomeningeal disease or other malignancy. Patients who are receiving non-cytotoxic concurrent drug for their malignancy may be allowed on the study, provided that the non-cytotoxic drug was started for at least 4 weeks prior to entry into the study and that no apparent toxicity from the non-cytotoxic drug is evident.
  3. Clinical evidence of obstructive hydrocephalus or compartmentalization of CSF flow.
  4. Patient has previously received anthracycline therapy up to the following cumulative doses: doxorubicin >/= 550 mg/m^2 (>/= 450 mg/m^2 if patient has had prior chest radiotherapy), epirubicin >/= 1000 mg/m^2 (>/= 800 mg/m^2 if prior chest radiation), idarubicin >/= 150 mg/m^2 (>/= 130 mg/m^2 if prior chest radiotherapy) and daunorubicin >/= 550 mg/m^2 (>/= 400 mg/m^2 if prior chest radiotherapy).
  5. Patients on anticonvulsant medications or other types of medications which are known liver-enzyme inducers.
  6. Patients who are pregnant or breast feeding, or adults (male or female) of reproductive potential not employing an effective method of birth control (such as oral, implantable, or injectable contraceptives ) (Women of childbearing potential must have a negative serum pregnancy test within 72 hours prior to administration of RTA 744 Injection)
  7. Total urinary protein in 24 hours urine collection > 500 mg
  8. Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study: 1) Uncontrolled diabetes (patients diagnosed with Type 1 or Type 2 diabetes who are currently under treatment by a physician for this condition and are not able to control blood sugars with management for glucose levels above 250 mg/dL). 2) Active or uncontrolled infection. 3) Acute or chronic liver disease (i.e., hepatitis, cirrhosis). 4) Confirmed diagnosis of HIV infection
  9. Impaired cardiac function, other significant prior cardiac disease or arrhythmia of any type, including any of the following: 1) LVEF < 45% as determined by MUGA scan or echocardiogram. 2) Complete left bundle branch block. 3) Obligate use of a cardiac pacemaker. 4) ST depression of > 1mm in >/= 2 leads and/or T wave inversions in >/= 2 contiguous leads. 5) Congenital long QT syndrome.
  10. 9. (continued) 6) History or presence of ventricular or atrial tachyarrhythmias. 7) Clinically significant resting bradycardia (< 50 beats per minute). 8) QTc > 480 msec on screening ECG. 9) Uncontrolled high blood pressure(>140/90), history of labile hypertension, or history of poor compliance with an antihypertensive regimen. 10) Unstable angina pectoris. 11) Symptomatic congestive heart failure.
  11. Myocardial infarction </=6 months prior to starting study drug. Patients with a history of CHF or arrhythmias
  12. Patients who are taking therapeutic doses of anticoagulant therapy (prophylactic dosing is allowed.)
  13. Patients who have received the following types of prior or concurrent therapy, or who have not recovered from the toxic effects of such therapy: 1) investigational drugs less than 4 weeks prior to entry on this study. 2) intrathecal chemotherapy within 2 weeks prior to entry into this study. 3) systemic cytotoxic chemotherapy within 4 weeks prior (6 weeks for nitrosourea or mitomycin-C or 2 weeks for vincristine) to entry on this study. 4) radiation therapy within 2 weeks prior to entry on this study. 5) any medication known to cause QT interval prolongation.
  14. Patients who have had any surgery, including resection of a brain tumor within 2 weeks prior to entry on this study
  15. Patients unwilling to or unable to comply with the protocol
  16. Patients who have a contraindication to MRI imaging (cardiac pacemaker, other ferromagnetic metal implants, claustrophobia not amenable to conscious sedation, and obesity greater than 300 lbs).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00512460

Locations
United States, Texas
U.T.M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Reata Pharmaceuticals, Inc.
Investigators
Principal Investigator: Morris D. Groves, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00512460     History of Changes
Other Study ID Numbers: 2006-0506
Study First Received: August 3, 2007
Last Updated: July 26, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Neoplastic Meningitis
Leptomeningeal Disease
Solid Tumor
Lymphoma
Leukemia
Brain Tumor
RTA 744

Additional relevant MeSH terms:
Lymphoma
Leukemia
Neoplasms
Brain Neoplasms
Meningitis
Meningeal Carcinomatosis
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Central Nervous System Infections
Meningeal Neoplasms

ClinicalTrials.gov processed this record on September 30, 2014